Erectile dysfunction, type 2 diabetes, and cardiovascular disease: a narrative review and insights from a global real-world cohort analysis

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Abstract
Background: Erectile dysfunction (ED) is highly prevalent among men with type 2 diabetes mellitus (T2DM) and reflects systemic vascular and metabolic dysfunction. Shared mechanisms include endothelial dysfunction, oxidative stress, inflammation, autonomic neuropathy, and hypogonadism. Therefore, ED may function not only as a complication of T2DM but also as an early clinical marker of cardiometabolic disease. Objective: This narrative review summarizes current evidence on the epidemiology, mechanisms, and cardiometabolic implications of ED in men with T2DM, and evaluates the impact of major cardiometabolic therapies on erectile function. A real-world cohort study was conducted using the TriNetX Global Collaborative Network, a large federated electronic health record database comprising healthcare organizations across multiple countries. Content: ED is closely linked with hypertension, obesity, dyslipidaemia, heart failure, ischemic heart disease, and stroke in men with T2DM, reflecting shared microvascular and macrovascular diseases. Cohort and real-world studies indicate a strong bidirectional relationship: poor cardiometabolic control worsens erectile function, whereas improvements in glycaemia, weight, blood pressure, and lipids are associated with higher International Index of Erectile Function (IIEF) scores. Using data from the TriNetX Global Collaborative Network, large-scale real-world analyses further demonstrate that the coexistence of ED and T2DM substantially increases cardiovascular risk. In a propensity-score-matched cohort (>200,000 individuals per group), men with ED and T2DM had higher risks of ischemic heart disease (15.7% vs. 11.5%, OR: 1.44; 95% CI 1.41-1.46), stroke (OR 1.45; 95% CI 1.42-1.48), peripheral artery disease (OR 1.38; 95% CI 1.35-1.41), and heart failure (8.4% vs. 4.9%, OR 1.78; 95% CI 1.74-1.81). Conversely, among individuals with T2DM, the presence of ED was associated with increased ischemic heart disease, stroke, and peripheral artery disease. Mechanistic and clinical data suggest heterogeneous treatment effects: GLP-1 receptor agonists and SGLT2 inhibitors show promising vascular benefits with mixed erectile outcomes, whereas ARBs and finerenone appear favorable compared with older agents associated with sexual adverse effects. Conclusion: ED in T2DM should be regarded as a clinically relevant marker of systemic vascular disease. Routine assessment may enhance cardiovascular risk stratification and motivate earlier, comprehensive risk-factor intervention. Future prospective and randomized studies with erectile function as a predefined endpoint are needed.

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